1. Field of the Invention
The present invention relates to a device, system, and method for delivery of ions from ion sources to a mass spectrometer to perform mass spectroscopy.
2. Discussion of the Background
Ion sources represent an important component of a mass spectrometer (MS). Atmospheric Pressure (AP) ion sources are used in modem analytical mass spectrometry. AP ion sources produce ions under ambient atmospheric conditions outside the vacuum of a mass spectrometer instrument. Atmospheric pressure chemical ionization APCI sources, as described by Bruins, in Mass Spectrom. Rev. 1991, vol. 10, beginning at p. 53, the entire contents of which are incorporated herein by reference, produce ions of volatile analytes with molecular masses 1-150 atomic mass units or Daltons (DA). Electrospray ionization (ESI) sources, as described in Yamashita, et al., J. Chem. Phys. 1984, vol. 88, pp. 4451 and Fenn, et al., Science 1989, vol. 246, p. 64-71, the entire contents of each reference are incorporated herein by reference, are used in analytical biochemistry to transfer heavy molecular ions (with masses up to several hundred thousand Da) intact from a liquid analyte solution to the gas phase for subsequent mass analysis. Further, an atmospheric pressure matrix assisted laser desorption ionization source (AP MALDI), as described in U.S. Pat. No. 5,965,884, the entire contents of which are incorporated herein by reference, produces ions of heavy biomolecules under normal atmospheric pressure conditions by laser irradiation, desorption, and ionization of analyte/matrix solid microcrystals.
AP ion sources are more accessible than xe2x80x9cinternalxe2x80x9d vacuum ion sources. In an AP ion source, sample ionization takes place outside the MS instrument itself The gas/liquid/solid sample delivery (or loading) takes place under normal laboratory atmospheric pressure condition. Ions produced under atmospheric pressure by an AP ion source are introduced into the vacuum chamber of mass spectrometer through an atmospheric pressure interface (API). Typically, the API consists of several stages of differential pumping separated by gas apertures.
In one approach as described in Horning et. al., Anal. Chem. 1973, vol. 455, pp. 936-943, the entire contents of which are incorporated herein by reference, a pinhole orifice in a thin membrane-type flange separates an atmospheric pressure region from an initial vacuum stage of the MS instrument (typically at a pressure of 0.1-5 mTorr). Ions leak through the pinhole into the mass spectrometer.
In another approach, as described in Whitehouse et al., Anal. Chem. 1985, vol. 57, pp. 675-679, the entire contents of which are incorporated herein by reference, an intermediate pumping chamber typically at a pressure of (0.1-5 mTorr) is connected via a capillary tube, typically having an inner diameter of 0.1-1.0 mm. The capillary tube is frequently heated to a temperature of 80-250xc2x0 C. for ion desolvation. The heated capillary tube delivers atmospheric pressure ions to the vacuum of the mass spectrometer, as described in U.S. Pat. Nos. 4,977,320 and 5,245,186, the entire contents of which are incorporated herein by reference.
A capillary tube can be used in modern commercial and scientific MS instruments. Ions produced at atmospheric pressure can be effectively transported through metal or insulating capillaries as long as 15 meters. Ion diffusion toward the walls of the capillary tube during transport through the tube represents an ion loss factor. However, the transport of heavy ions in capillary tubes is effective because heavy ions, having lower diffusion coefficients than light ions, do not diffuse as rapidly to the walls of the capillary.
Ion losses in a capillary tube depend mainly on the ion residence time inside the capillary. If a gas flow through a capillary is fixed, the loss of ions to the walls of the capillary tube will depend mainly on the capillary length, and not on the capillary diameter. Both metallic and insulating (e.g., glass) capillaries show similar ion transport properties. The process of ion transport by viscous gas flow through capillaries is described in B. Lin and J. Sunner, J. Am. Soc. Mass Spectrom. 1994, vol. 5, pp. 873-885, the entire contents of which are incorporated herein by reference.
FIGS. 1 and 2 represent schematically two APIs for introducing ions from an atmospheric pressure ion source into a mass spectrometer. As shown in these figures, the API can be include either an inlet capillary tube 2 (as shown in FIG. 1) or a pinhole orifice 3 (as shown in FIG. 2). The inlet capillary tube 2 as shown in FIG. 1 is located on a MS inlet flange 4a. The pinhole orifice 3 as shown in FIG. 2 is located on a MS inlet flange 4b. 
In FIG. 1, an electrospray ion (ESI) source 5 is placed into an atmospheric pressure region 6 close to an inlet orifice 7 of the inlet capillary tube 2. The capillary tube 2 is attached to the inlet flange 4a of the mass spectrometer. The pressure in vacuum chamber behind the inlet capillary tube 2 is typically 1-5 Torr.
In FIG. 2, the ESI source 5 is placed into the atmospheric pressure region 6 close to the pinhole orifice 3. The pinhole orifice 3 is attached to the inlet flange 4b and separates the atmospheric pressure region 6 from a first pumped region 8 behind the inlet flange 4b. A skimmer 9 separates the first pumped region 8 from a second pumped region 10. In the second pumped region 10, the pressure is several orders of magnitude lower than in the first pumped region 8. Typically, a gas curtain is used to prevent large droplets from the ESI source from blocking the inlet orifice 3. The gas curtain includes a gas curtain electrode 11. A gas counterflow flows as shown by the arrow in FIG. 2 between the gas curtain electrode 11 and the inlet flange 4b restricts large droplets from reaching the pinhole orifice 3. In FIGS. 1 and 2, the ESI source 5 is placed as close as possible to the respective inlet orifices 3 or 7 in order to enhance mass spectrometer ion collection.
Because an atmospheric pressure ion source is an external part of a mass spectrometer, in theory a MS instrument can work with a number of the existing ion sources. However, commercial MS instruments are designed to accommodate only one or two particular ion sources. Usually, commercial MS instruments will accommodate only an ESI or an APCI source. Other atmospheric pressure ion sources such as the AP MALDI source previously noted are not readily accommodated.
As shown in FIG. 3, the AP MALDI source includes a target plate 11, a laser beam 12 which irradiates the target plate 11 via mirror 13 which reflects the irradiated laser beam onto a position of the target plate where desorption and ionization of adsorbed species occurs. A detailed description of an AP MALDI source can be found in U.S. Pat. No. 5,965,884, the entire contents of which has been previously incorporated herein by reference. In FIG. 3, the physical size and geometric arrangement of the laser optics and the size of the target plate 11 do not permit the placement of an AP MALDI source in close proximity to the inlet orifice 7 of the inlet capillary tube 2. U.S. Pat. No. 5,965,884 describes a modification to the API which enables an AP MALDI ion source to interface to a mass spectrometer. In this modification, a flange with an inlet orifice is attached to a mass spectrometer and becomes an integral part of the mass spectrometer instrument. As such, the interchangeability to other atmospheric pressure sources such as ESI and APCI sources is complex and time-consuming. To change the flange requires, venting the mass spectrometer, installing another flange, and evacuating the mass spectrometer back to a low operating pressure.
In conventional approaches, variations in the pressure and temperature conditions in front of the inlet capillary tube 2 or the pinhole orifice 3 change the transport characteristics into the mass spectrometer and thus change the sensitivity of the mass spectrometer. Thus, one object of the present invention is to provide a device that delivers ions produced from one or more remote ion sources to an inlet orifice of a mass spectrometer in such a way that the delivery does not disturb significantly the physical conditions (pressure, temperature) around the inlet orifice to the mass spectrometer.
Another object of the present invention is to provide a CIDD which can deliver over a determined distance ions produced from various ion sources to an inlet orifice of a mass spectrometer. Further, in one embodiment of the present invention, the CIDD is detachable which enables different ion sources to be attached to the mass spectrometer without disruption to the operation of the mass spectrometer.
Advantageously, the CIDD of the present invention can work at an arbitrary temperature, can support temperature differentials across a longitudinal length, and can support pressure differentials across a longitudinal length of the CIDD.
Thus, it is another object of the present invention to provide a CIDD which permits a higher than atmospheric-pressure source to be coupled to the mass spectrometer without affecting the sensitivity of the mass spectrometer. In the CIDD of the present invention, a stream of gas flows through one or more transport tubes. Ions are transported through the CIDD as a result of a pressure drop between an inlet orifice and a connection port of the CIDD. The pressure differential can be small compared with atmospheric pressure.
Still another object of the present invention is to provide a CIDD which permits desolvation of ions in a heated section of the CIDD prior to arrival of the transported ions to the inlet orifice of the mass spectrometer, and more importantly permits arrival of the ions to the inlet orifice to the mass spectrometer without affecting the standard temperature condition.
Another object of the present invention is to provide a gas switch in the CIDD to enable the mass spectrometer to sample from different ion sources.
Still a further object of the present invention is to deliver ions at an arbitrary temperature including ambient temperature conditions.
Another object of the present invention is to provide a reaction vessel in the CIDD in order to allow chemical mixing and reactions to occur between ions from different ion sources.
These and other objects are achieved in a system and method for mass spectrometry in which the system includes at least one ion source which produces ions, a mass spectrometer having an inlet orifice configured to accept the ions, and a capillary ion delivery device which detachably interfaces to the inlet orifice of the mass spectrometer. The method includes producing ions from the ion source, transporting the ions from the ion source to the inlet orifice of the mass spectrometer via the capillary ion delivery device, and mass analyzing the ions in the mass spectrometer.